Our major objectives of this study are to better understand the nature of genetic mechanisms in controlling colorectal epithelial cell proliferation and differentiation; and to gain increased insight into alterations in these mechanisms which accompany chemically induced neoplastic transformation. It is proposed to continue study on the biological and biochemical changes in nuclear function of the colonic epithelium from normal rats and with precancerous and malignant lesions resulting from exposure to carcinogens. We plan to study the phosphorylation of nuclear phosphoproteins and histones, specificities of nuclear phosphoprotein kinases, heterogeneity of DNA polymerases and the properties of other enzymes involved in the process of chemical carcinogenesis.